UMEM Educational Pearls - Toxicology

Scombroid is caused by ingestion of preformed histamine on skin of fish.

• Naturally occurring histidine on scaly fish converted to histamine by surface bacteria - often fish left out too long, refrigeration will prevent the conversion.
• Bacteria responsible are Morganelli morganii and K. pneumoniae
• Fish: tuna, mahi mahi, amberjack, bonito, mackerel, albacore
• Fish usually appears normal though meat may tast peppery
• Patient presents minutes/hrs flushed, urticaria, HA, N/V
• Self-limited and improve within hrs even without treatment
• Antihistamines and rarley epinephrine will be needed

We are all familiar with the classic ECG abnormalities caused by the sodium channel blocking properties of tricyclic antidepressants (QRS interval widening, R wave in aVR, S wave in I and aVL, and rightward deviation in terminal 40 msec of QRS). Here are some other medications that also block cardiac sodium channels in a similar manner:

• Cocaine
• Diphenhydramine
• Cyclobenzaprine (Flexeril)
• Carbamazepine (Tegretol)
• Phenothiazines
• Propoxyphene
• Class 1A antidysrhythmics (quinidine, procainamide, disopyramide)
• Class 1C antidysrhythmics (encainide, flecainide, propafenone, moricizine)
• Amantadine

It is likely that you will be asked questions about the huge recall by McNeil..

It stems from complaints received of black particles found in the pediatric liquid formulation, which are manufactured at one facility in Fort Washington, PA.  The FDA inspected the plant and found inadequate quality standard testing and facilities. Either there were potential bacteria in one of the raw products (which did not make it to the final product), or the final concentrations were stronger than specified.

McNeil recalled forty-three formulations of pediatric liquid tylenol, zyrtec, motrin and benadryl. Generic versions are unaffected.

Complete recall information:

www.mcneilproductrecall.com

For more information and links:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm210442.htm

Several drugs and compounds may be radiopaque on an abdominal radiograph. This may be helpful in an overdose to determine ingestion or amount ingested. Attached is a pic a patient that ingested potassium sustained release tables.

The mneumonic CHIPES will help you remember which are:

C - Calcium Carbonate, chloral hydrate

H - Heavy metal - like Mercury, lead

I - Iron and Iodine

P - Phenothiazines (compound that has S(C₆H₄)₂NH in it), drugs that include: antipsychotics like chlorpromazine (thorazine) and antiemetics like prochlorperazine (compazine)

E - Enteric coated pills

S - Solvents [halogenated ones like chloroform] and Sustained Release preparations [Lithobid and K-Dur]

Attachments

KCl_patient_1.JPG (182 Kb)

Many drugs/toxins cause nystagmus, particularly in overdose.  Vertical, horizontal, or rotary nystagmus may be noted.

The most common drug/toxin overdoses that cause nystagmus are the following:

• Anticonvulsants (phenytoin, carbamazepine, valproic acid, lamotrigine, topiramate)
• Ethanol
• Lithium
• Dextromethorphan
• Phencyclidine (PCP)
• Ketamine
• Lysergic acid diethylamide (LSD)

Show References

When you draw a urine toxicology screen it can mislead more often than help you. Here is a quick list of the test followed by some medications that cause false positives - when in doubt, call your lab to find out specifics since results will vary lab to lab:

TCA - diphenhydramine, carbamazepine, cyclobenzaprine (side note: TCA screen should never be used to determine TCA toxicity, your ECG and physical exam should be enough to determine if the patient is toxic from TCA

Cocaine - the most accurate test on the screen, positive for up to 5 days

PCP - dextromethorphan and ketamine can turn it positive

Amphetamines - pseudoephedrine, ephedrine, phenylephrine and many other OTC cough decongestants can as well, the worst screening test with the largest number of false positives

According to the Food Allergy and Anaphylaxis Network, the eight most common food allergies, which account for 90% of the food allergies in the U.S., are: dairy, soy, wheat, shellfish, fish, peanut, tree nut, and egg.

Several medications are formulated with these ingredients and should be avoided in patients with reported allergies.

• Propofol is a lipid emulsion that contains egg.  Avoid in patient with hypersensitivity to eggs, egg products, soybeans, or soy products.
• Ipratropium ± albuterol (Atrovent, Combvient®) inhalers may contain soy lecithin.  This can cause allergic reactions in patients with allergy to soy lecithin or related food products (e.g., soybean and peanut).  Nebulizer solutions (e.g., Duoneb®) seem to be free from this issue.
• Progesterone (Prometrium®) capsules contain peanut oil.

When a child is reported to be exposed to a rat poison it is commonly a long acting coumarin like brodifacoum. The rat usually eats the poison then during its traumatic little life will cause its own death by jumping and squeezing through a crack. When a human is exposed, this is the typical sequence of events:

1. Exposure (and when you usually see them in the ED)
2. 24-72 hrs later you will actually see an INR rise if actually ingested

Treatment is the same as for coumadin, vitamin K. However, do not start empirically since the patient will be committed to high doses of vitamin K for several months. Let the patient prove they have been poisoned which means they will require recheck of their INR 2-3 days later though they can be sent home with specific warning signs of anticoagulation.

With all of the post-transplant patients we see in the ED, a refresher on the toxicities associated with the most common immunosuppressant medications is warranted.

Cyclosporine (Sandimmune^® and Neoral^®/Gengraf^®) and tacrolimus (Prograf^®) are both calcineurin inhibitors that inhibit activation and proliferation of T-lymphocytes and IL-2.

-          Major concerns: Nephrotoxicity, drug interactions (CYP3A4)

-          Adverse Effects:

o       Electrolyte abnormalities: ­K+, ¯Mg+, ­glucose

o       CNS: HA, tremor (statistically higher with tacrolimus)

o       CV: HTN, ­ lipids (increased with cyclosporine)

o       End organ: hepatotoxicity, nephrotoxicity

o       Cosmetic (cyclosporine specific): hirsutism, gingival hyperplasia, acne

Sirolimus/Rapamycin (Rapamune^®) is an M-tor inhibitor that inhibits T-lymphocyte activation and proliferation.

-          Major concerns: Drug interactions (CYP3A4)

-          Adverse Effects:

o       Delayed wound healing

o       Leucopenia, thrombocytopenia

o       Hypercholesterolemia

CARBAPENENEMS

• Broadest spectrum of activity of all classes
• Imipenem has slightly better gm + activity; lowers seizure threshold
• Meropenem has slightly better gm - activity
• Ertapenem does not cover Pseudomonas
• Doripenem has the most activity against Pseudomonas
• May use in PCN allergic patients (cross reactivity lower than previously thought)

TIGECYCLINE

• Has broad coverage, but does not cover Pseudomonas
• Bacteriostatic; derivative of tetracycline
• Does NOT require renal dosing
• Higher mortality in VAP than other agents; do not use for intra-abdominal infections (poss higher risk of perforation)

AMIKACIN

• Has antipseudomonal activity
• Used in combination with other agents for MDR (multi-drug resistant) bacteria
• Causes nephrotoxicity and ototoxicity

COLISTIN

• Bacteriocidal against many MDR gram - bacteria
• Not active against Proteus, Provincia, Burkholderia, Neisseria, or Serratia
• Nephrotoxicity and ototoxicity reported

Show References

Apologies - last few bullets were cutoff - Continuing - Prophylaxis against RCIN has been attempted with the following:

• IV saline infusion
• Sodium Bicarbonate bolus
• IV acetylcysteine infusion

No one therapy has been show to have superior efficacy.

Radiocontrast Induced Nephropathy (RCIN)

• Occurs within 24 hrs of administration followed by oliguric phase
• Usually improves within a week and rarely needs dialysis
• Initial injection is an osmotic load, leads to volume expansion and diuresis. Follwed by intense vasoconstriction suggesting possible ischemic role in pathophysiology.
• There is also a direct toxic effect to the kidneys however
• High Risk patients: HTN, DM,  Chronic Renal Insuff, Bence Jones proteinuria and large injections of IV dye
• Possible prophylaxis: There is almost no data studying this effect in the Emerg Dept patient. One trial look at IV acetylcysteine in the Emergent CT (RAPPID trial) did show benefit but has flaws within the study. IV hydration and sodium bicarbonate

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Quinolone Induced Deliurim

Just to give you another reason NOT to give a quinolone - aside from the C. diff. This adverse effect occurs with quinolones unlike many other antibiotics. It can prolong hospital stay, cause falls and further medical work ups. Some risk factors are:

• Elderly
• Renal Insufficiency
• Benzodiazepine dependence (will actually precipitate withdrawal since quinolones displace the BDZ from the receptor - you have probably done this to a patient if you think about it, that may be why they went crazy)
• Epilepsy - can cause seizures especially with NSAIDs

As we are now into the winter months, exposures to ethylene glycol (antifreeze) and methanol (windshield washer fluid) increase.  Here is a good mnemonic for sorting through an anion gap metabolic acidosis:

C – cyanide, carbon monoxide
A – alcoholic ketoacidosis, acetaminophen (massive OD)
T – toluene (chronic from glue sniffing)
M – methanol, metformin
U – uremia
D – diabetic ketoacidosis
P – propofol infusion syndrome, propylene glycol, paraldehyde
I – iron, isoniazid, ibuprofen (massive OD)
L – lactic acidosis
E – ethylene glycol
S – salicylates, starvation ketoacidosis

SUCCIMER (DMSA)

• An oral agent used for the chelation of heavy metals, such as LEAD, ARSENIC and MERCURY
• Forms a water soluble agent that chelates the heavy metal, which are renally excreted
• Most common side effects are rashes, urticaria and GI
• A serious adverse effect is neutropenia, which is rare

A quick christmas one:

The Christmas Rose (Helleborus niger)

Actually containes cardioactive steroids - eating it will help your A fib with RVR as it will act like digoxin, as well as kill like it.

Attachments

christmasrose.jpg (30 Kb)

Here is a table adapted from Goldfrank's Textbook of Toxicologic Emergencies 8th Edition - Drugs that May Induce Parkinsonism. MPTP is the story that everyone hears about and actually has links to Maryland. In 1976, Barry Kidston, a 23-year-old chemistry Maryland graduate student, synthesized MPPP (Meperidine or Demerol) incorrectly and injected the result. It was contaminated with MPTP, and within three days he began exhibiting symptoms of Parkinson's disease. Ooops - permanent.

Reversible

• Chemotherapeutics (several)
• Cyclosporine
• Calcium Channel Blockers
• Dopaminergic withdrawal
• Kava Kava (with manganese)
• Progesterone
• Sertraline
• Valproic Acid
• Trazodone

Irreversible

• Carbon Monoxide
• Cyanide
• Heroin
• Manganese
• MPTP